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PIGEON-FEATHER datasets, extracting site-resolved energetic information from HX/MS experiments

ABSTRACT: We present PIGEON-FEATHER, a method for calculating free energies of opening (∆Gop) at single- or near-single-amino acid resolution for protein ensembles of all sizes from hydrogen exchange/mass spectrometry (HX/MS) data. PIGEON-FEATHER disambiguates and reconstructs all experimentally measured isotopic mass envelopes using a Bayesian Monte Carlo sampling approach. We applied PIGEON-FEATHER to reveal how E. coli and human dihydrofolate reductase (ecDHFR, hDHFR) have evolved distinct conformational ensembles tuned to their catalytic cycles. We showed how two competitive inhibitors of ecDHFR arrest its ensemble in different ways, only one of which is compatible with vertebrate DHFR orthologs. Finally, we uncovered how the lac repressor (LacI) ensemble responds to binding its inducer molecule and operator DNA to regulate transcriptional activation.

INSTRUMENT(S): maXis

ORGANISM(S): Escherichia Coli

SUBMITTER: Chenlin Lu

LAB HEAD: Anum Glasgow

PROVIDER: PXD057539 | Pride | 2024-11-05

REPOSITORIES: Pride

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			Action	DRS
	11-18-lacI-pooled-CLEAN.csv	Csv
	20221118-dna-msms.mgf	Mgf
	20221118-iptg-msms.mgf	Mgf
	20230114-lacI_DNA.mgf	Mgf
	20230114-lacI_IPTG.mgf	Mgf

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PIGEON-FEATHER datasets, extracting site-resolved energetic information from HX/MS experiments

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